What is pre-approval and unlicensed access to medicines?

Typically, there are three ways in which patients can get access to a medicine; through a clinical trial, when it is commercially available, or via a pre-approval / unlicensed medicines access program. The terms ‘Pre-approval’ and ‘unlicensed medicines access’ refer to the regulatory mechanisms which allows a drug manufacturer (pharmaceutical company or biotech company) to make a medicine available to patients, in a country where it is not formally approved or commercially available and where there are no accessible clinical trials or suitable alternative treatments.

Pre-approval / unlicensed medicines access is known by a variety of other terms, such as; expanded access, early access, compassionate use, named patient program, managed access program etc.. Some of these terms are specific to a particular country (see table below), but often they are used interchangeably by people and companies alike, resulting in confusion (e.g. the perception that ‘compassionate use’ must mean free-of-charge provision of a medicine). For these reasons, Inceptua prefers to utilize the umbrella terms of ‘pre-approval access’ when a medicine has not been approved anywhere in the world, and ‘medicines access’ when a medicine has been approved somewhere, but not in the country of intended use.

Why is there pre-approval / unlicensed medicines?

Pre-approval and unlicensed medicines access really began in earnest during the HIV epidemic in the 1980’s. At that point the USA FDA put in place structures to support patients seeking access to medicines prior to their approval. Since then, the majority of countries have adopted such approaches.

The focus on pre-approval / unlicensed medicines access has increased in recent years as company pipelines are skewed towards those disease areas of high unmet need (e.g. rare diseases and oncology) which often see demand for access long before commercial availability. This, combined with a much greater ability to access information about products under development, has driven demand for companies to put such programs in place.

Most countries passed laws to allow their citizens to gain access to medicines which are not available in their country, on the basis that patients in need should not be disadvantaged in their ability to access a medicine which may help them.

The reasons why these medicines might not be available in a country include; a drug shortage (where a drug producer cannot manufacture enough drug to supply all the patients who need it), the drug is still undergoing clinical development and is not yet approved in any country, or the drug is not ‘approved or available’ in the patient’s specific country (perhaps because the drug manufacturer does not think it is commercially-viable to launch the drug in that country e.g. if there are very few patients who need the drug), or the drug is not yet approved in that country.

This latter scenario is common. Pharmaceutical companies and biotech companies do not launch their medicines in all countries at the same time, for practical and financial reasons. This means that there is a staggered launch of a new medicine, perhaps taking several years before it is available in all countries where it will be sold. In this situation, the drug manufacturer may decide to put in place a ‘pre-approval / unlicensed medicines access program’ to allow patients in all countries in question to access the medicine at the same time, whilst the manufacturer goes through the long process of making it formally available for use/sale in each country

Is pre-approval / unlicensed access ethical?

Yes. Formal pre-approval / unlicensed medicines access to a medicine is highly ethical, and is regulated by the appropriate authorities in each country. Additionally, it is conducted either directly by the pharmaceutical / biotech company themselves, or in partnership with a specialist organization. This ensures that the medicine is being made available according to the appropriate laws and regulations in each country.

Many people would argue that allowing patients to access a medicine that they would otherwise not be able to, is ethical in itself.

Over the last 10 years there have been many developments in terms of the regulations underpinning pre-approval / unlicensed medicines access. The majority of these developments have been positive, and intended to simplify the process for physicians and patients. Pre-approval / unlicensed medicines access is viewed as an important method of access outside of the commercial supply route and the clinical trial route

Are there any restrictions around pre-approval / unlicensed medicines access?

As a base case, there are no ‘restrictions’ around pre-approval / unlicensed medicines access. So long as the regulations are followed, the regulators generally allow doctors to prescribe any medicine which in their ‘clinical judgement’ may benefit a patient. The regulators do not normally contest the doctor’s decision to prescribe. Although they may want to see some quality, safety or efficacy data prior to allowing the medicine to be imported and prescribed for a specific patient.

Some country regulations place some form of stipulation on the manufacturer of the drug if they make it available pre-approval. Such stipulations can include; a requirement to submit regular safety reports to the regulatory agency in the country where the medicine is used.

Does a company have to allow pre-approval / unlicensed medicines access?

No. A company is not obligated to allow pre-approval / unlicensed medicines access to any of its medicines. The 21st Century Cures Act of the USA mandates that pharmaceutical companies must have a public statement on their website about their approach to pre-approval / unlicensed medicines access. Although this is not a requirement outside of the US, it could be argued that such statements should be the norm, as they allow patients and physicians to understand if a medicine is available pre-approval, and also to understand the reasons why, if it is not.

Considering an access program for your asset? Ask Inceptua!